Analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) have been used for many years for the treatment of pain and/or fever. This dual action is sometimes contraindicated. In many instances pain needs to be controlled without masking the symptomatic fever (e.g., the postoperative period). These drugs can also cause hepatotoxicity, particularly after ingestion of large doses or chronic use of smaller doses (especially when liver function have has been compromised) that can lead to death. Therefore, there is a need for new more selective compounds with greater pharmacological potency and little hepatotoxic, nephrotoxic, or antipyretic effects. St Charles is exploring a series of new and proprietary derivatives of acetaminophen. In preliminary studies, one of these compounds demonstrated high analgesic activity free from antipyretic activity and hepatotoxicity. In this SBIR project we propose to further characterize these initial compounds and to explore the series to optimize their physical, chemical and biological properties. The feasibility experiments in phase I will identify lead candidate drug(s) that we will further test and develop in phase II for the treatment of postoperative pain, pain associated with pneumonia, chronic pain, phantom limb pain, and for analgesic treatment where acetaminophen is contraindicated. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE